Regulation of functions of drug transporters in renal tubules by inflammatory cytokines and implication of its significance

在脂多糖（LPS）制备的炎症大鼠模型中，甲氨蝶呤（MTX）的血浆清除率降低了约50%。肾小球滤过和小管分泌参与了LPS对MTX肾脏清除率的降低。LPS大鼠的肾组织/血浆浓度比和肾组织到小管腔的外排清除率也下降，与肾脏中有机阴离子转运体（rOAT1、rOAT3、rMRP2、rMRP4）表达水平下降相当。综上所述，lps处理大鼠MTX的肾脏清除率明显降低，肾小球滤过减少以及肾小管中有机阴离子转运蛋白表达水平下降是其原因。

Plasma clearance of methotrexate (MTX) decreased about 50% in the inflammatory rat model, which is prepared by the administration of lipopolysaccharide (LPS). Involvement of glomerular filtration as well as tubular secretion were suggested in the decreased renal clearance of MTX by LPS. Renal tissue/plasma concentration ratio and efflux clearance from renal tissue to the tubular lumen also decreased in LPS rats, and were comparable to the decreased expression levels of organic anion transporters (rOAT1, rOAT3, rMRP2, rMRP4) in the kidney. In conclusion, the renal clearance of MTX markedly decreased in the LPS-treated rats and the contribution of decreased glomerular filtration as well as decreased expression levels of organic anion transporters in the renal tubules were suggested.